title: Aspartate as a selective NMDA receptor agonist in cultured cells from the avian retina.
abstract: Although glutamate is considered the natural neurotransmitter that mediates excitatory function in the CNS, other active natural compounds can also drive the functional activation of excitatory amino acid receptors (EAAR). L-aspartate is the most likely neurotransmitter to mimic the actions of glutamate. Here we show that L-aspartate promotes the release of GABA acting selectively on the NMDA receptor subtype. Retina cell cultures, when exposed to excitatory amino acids (EAA), release [3H] GABA previously incorporated by the cells. Both L-glutamate and L- and D-aspartate at 100 microM concentration, promote the release which can be mimicked by kainate and NMDA. While aspartate-induced release of [3H] GABA occurs in the presence of 1 mM Mg2+, NMDA (100 microM) promotes the release only when Mg2+ is omitted from the superfusing medium. However, in the absence of Mg2+ the efficacy of 1- and d-aspartate (100 microM) to activate [3H] GABA release increases by a factor of 2 when compared to the release observed in the presence of 1 mM Mg2+. NMDA and aspartate induced release of [3H] GABA is completely inhibited by 10 microM MK-801 and is not affected by CNQX (100 microM). In the presence of Mg2+, aspartate-induced release of [3H] GABA is also completely inhibited by MK-801 (10 microM) and is not significantly affected by CNQX (100 microM). The [3H] GABA release induced by kainate (100 microM) is fully inhibited by CNQX (100 microM) and is not affected by MK-801 (10 microM). Our results indicate that in the retina, l-aspartate modulates its excitatory function on a set of GABAergic cells via the selective activation of NMDA receptors. The fact that L- and D-aspartate (but not D-glutamate) induce the release of GABA even in the presence of Mg2+ suggests that the electrogenic uptake of aspartate is required to lower the affinity of the NMDA channel for Mg2+. The observation that D-glutamate (200 microM), which is not taken up by the cells, activates the efflux of GABA only when Mg2+ is omitted from the incubating medium, supports this possibility.
authors.affiliation: Laboratório de Neuroquímica, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: R C
authors.initials: RC
authors.lastname: Kubrusly
authors.forename: M C
authors.initials: MC
authors.lastname: de Mello
authors.forename: F G
authors.initials: FG
authors.lastname: de Mello
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000187:drug effects / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D008274:Magnesium; D007608:Kainic Acid